关键词: F8 gene genetic diagnostics hemophilia A pathogenic variant

Mesh : Humans Hemophilia A / genetics Factor VIII / genetics Mutation Chromosome Inversion Nucleotides Russia

来  源:   DOI:10.3390/genes14020260

Abstract:
Hemophilia A (HA) is one of the most widespread, X-linked, inherited bleeding disorders, which results from defects in the F8 gene. Nowadays, more than 3500 different pathogenic variants leading to HA have been described. Mutation analysis in HA is essential for accurate genetic counseling of patients and their relatives. We analyzed patients from 273 unrelated families with different forms of HA. The analysis consisted of testing for intron inversion (inv22 and inv1), and then sequencing all functionally important F8 gene fragments. We identified 101 different pathogenic variants in 267 patients, among which 35 variants had never been previously reported in international databases. We found inv22 in 136 cases and inv1 in 12 patients. Large deletions (1-8 exons) were found in 5 patients, and we identified a large insertion in 1 patient. The remaining 113 patients carried point variants involving either single nucleotide or several consecutive nucleotides. We report herein the largest genetic analysis of HA patients issued in Russia.
摘要:
血友病A(HA)是最广泛的,X-linked,遗传性出血性疾病,这是F8基因缺陷的结果.如今,已经描述了超过3500种导致HA的不同致病变异。HA中的突变分析对于患者及其亲属的准确遗传咨询至关重要。我们分析了来自273个具有不同形式HA的无关家庭的患者。分析包括内含子反转测试(inv22和inv1),然后对所有功能上重要的F8基因片段进行测序.我们在267例患者中鉴定出101种不同的致病变异,其中35个变体以前从未在国际数据库中报告过.我们发现136例患者中inv22例,12例患者中inv1例。在5例患者中发现了大缺失(1-8个外显子),我们在1例患者中发现了一个大的插入。其余113名患者携带涉及单个核苷酸或几个连续核苷酸的点变体。我们在此报告了俄罗斯发布的最大的HA患者遗传分析。
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